Although the action of the standard chemotherapeutic agent for the treatment of advanced colorectal cancer (5-fluorouracil or 5-FU) was improved significantly by combining it with leucovorin (LV), the improved response rate was associated with significant side-effects in approximately thirty percent of patients. In Fluoropyrimidines in Cancer Therapy, leading cancer researchers update and review the mechanisms of action and the therapeutic selectivity and efficacy of 5-FU, with and without LV and its prodrugs, in the treatment of colorectal cancer. Among the combination agents considered are Orzel (UFT/LV), 5-FU/Eniluracil (5-FU/EU), capecitabine (Xeloda), S-1, and a variety of thymidylate synthase inhibitors. The authors discuss the potential advantages and disadvantages of these varied drugs and their mode of administration. Based on the historical results with these agents when used alone, they also present a rationale for their results when used in combination with other agents.
Authoritative and integrative, Fluoropyrimidines in Cancer Therapy summarizes the latest preclinical and clinical experiences using fluoropyrimidines to treat colorectal cancer, delineates the underlying mechanisms and choices for therapy, describes the ongoing search to identify ever more effective and selective agents with novel mechanisms of action, and details the development of new mechanism-based combination therapies.

Klappentext

Leading cancer researchers update and review the mechanisms of action and the therapeutic selectivity and efficacy of 5-FU with and without leucovorin and its prodrugs in the treatment of colorectal cancer. Among the combination agents considered are UFT/LV, 5-FU/EU, capecitabine (Xeloda), S-1, and a variety of thymidylate synthase inhibitors. The authors discuss the potential advantages and disadvantages of these varied drugs and their mode of administration. Based on historical results with these agents when used alone, they also present a rationale for their results when used in combination with other agents.

Inhalt

Relative Role of 5-Fluorouracil Activation and Inactivation Pathways on its Cytotoxic Effects: Preclinical and Clinical Modulation G. J. Peters Dihydropyrimidine Dehydrogenase and Treatment by Fluoropyrimidines: Past and Future Directions Gérard Milano Biochemical Bases of the 5-Fluorouracil-Folinic Acid Interaction and of its Limitations: A Retrospective Analysis Richard G. Moran Molecular Mechanisms Regulating the Expression of Thymidylate Synthase John C. Schmitz, Ashwin Gollerkeri, Xiukun Lin, Jun Liu, and Edward Chu Regulation of Thymidylate Synthase Gene Expression and Drug Response: Posttranscriptional Regulation and Cell Population Density Bruce J. Dolnick Death Receptor Signaling in the Mechanism of 5-Fluorouracil Action Janet A. Houghton Circadian Rhythms in 5-Fluorouracil Pharmacology and Therapeutic Applications Francis Lévi Relevance of Scheduling to the Efficacy of 5-Fluorouracil Alone and in Combination with Other Agents Alberto F. Sobrero and Ornella Belvedere Noninvasive Studies of Fluoropyrimidines Walter Wolf, Cary A. Presant, and Victor Waluch Comparative Antitumor Activity of 5-Fluorouracil (5-FU) Prodrugs in Preclinical Model Systems: Role of Leucovorin and Dihydropyrimidine Dehydrogenase Inhibitors Shousong Cao, Gunnar Hapke, and Youcef M. Rustum Bimonthly 48-h Leucovorin and 5-Fluorouracil-Based Regimens in Advanced Colorectal Cancer Aimery de Gramont and Christophe Louvet Review on the Combination of Systemic and Locoregional Treatment for Colorectal Liver Metastases Roberto Labianca, Gianfranco Pancera, Marinella Mastore, Marina Garassino, Giordano D. Beretta, Paola Poletti, and M. Adelaide Pessi Fluoropyrimidines in Advanced Colorectal Cancer: A Review of Six Consecutive Meta-Analyses Pascal Piedbois and Marc E. Buyse The Mayo/NCCTGExperience with 5-Fluorouracil and Leucovorin in Adjuvant Advanced Colorectal Cancer Charles Erlichman, Richard M. Goldberg, and Daniel J. Sargent Fluoropyrimidines for the Adjuvant Treatment of Colorectal Cancer: The NSABP Experience Roy E. Smith, Eleftherios P. Mamounas, and Norman Wolmark Clinical Trials of UFT Leucovorin in Gastrointestinal Malignancies Paulo M. Hoff and Everardo D. Saad The Development of Oral UFT with and without Leucovorin Geert H. Blijham UFT in Elderly Patients with Colorectal Cancer Albert Abad and José Luis Manzano Clinical Trials of the Eniluracil/5-Fluorouracil Combination Hedy L. Kindler and Richard L. Schilsky Discovery and Preclinical Pharmacology of Capecitabine Hideo Ishitsuka Capecitabine, A Tumor-Targeting Oral Fluoropyrimidine: Molecular Rationale and Clinical Validation Dvorit Samid Capecitabine: A Rationally Developed Anticancer Drug Daniel R. Budman Preclinical and Clinical Practice of S-1 in Japan Tetsuhiko Shirasaka and Tetsuo Taguchi Preclinical and Clinical Practice of Low-Dose FP Therapy in Japan: Japanese Use of Low-Dose FP Therapy Tetsuhiko Shirasaka, Akihito Tsuji, Susumu Yamamitsu, and Tetsuo Taguchi